Reinfection of farm dogs following praziquantel treatment in an endemic region of cystic echinococcosis in southeastern Iran.

Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus eggs excreted from infected dogs. CE is endemic in the Middle East and North Africa, and is considered as an important parasitic zoonosis in Iran. It is transmitted between dogs as the primary definitive host and different livestock species as the intermediate hosts. One of the most important measures for CE control is dog deworming with praziquantel. Due to the frequent reinfection of dogs, intensive deworming campaigns are critical for breaking CE transmission. Dog reinfection rate could be used as an indicator of the intensity of local CE transmission in endemic areas. However, our knowledge on the extent of reinfection in the endemic regions is poor. The purpose of the present study was to determine E. granulosus reinfection rate after praziquantel administration in a population of owned dogs in Kerman, Iran. A cohort of 150 owned dogs was recruited, with stool samples collected before praziquantel administration as a single oral dose of 5 mg/kg. The re-samplings of the owned dogs were performed at 2, 5 and 12 months following initial praziquantel administration. Stool samples were examined microscopically using Willis flotation method. Genomic DNA was extracted, and E. granulosus sensu lato-specific primers were used to PCR-amplify a 133-bp fragment of a repeat unit of the parasite genome. Survival analysis was performed using Kaplan-Meier method to calculate cumulative survival rates, which is used here to capture reinfection dynamics, and monthly incidence of infection, capturing also the spatial distribution of disease risk. Results of survival analysis showed 8, 12 and 17% total reinfection rates in 2, 5 and 12 months following initial praziquantel administration, respectively, indicating that 92, 88 and 83% of the dogs had no detectable infection in that same time periods. The monthly incidence of reinfection in total owned dog population was estimated at 1.5% (95% CI 1.0-2.1). The results showed that the prevalence of echinococcosis in owned dogs, using copro-PCR assay was 42.6%. However, using conventional microscopy, 8% of fecal samples were positive for taeniid eggs. Our results suggest that regular treatment of the dog population with praziquantel every 60 days is ideal, however the frequency of dog dosing faces major logistics and cost challenges, threatening the sustainability of control programs. Understanding the nature and extent of dog reinfection in the endemic areas is essential for successful implementation of control programs and understanding patterns of CE transmission.

Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology.

Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex, and the impact of multiple interacting factors, such as age, co-morbidities and host immune response, is often poorly quantified. Mathematical modelling has been used for many years to gain insights into the complex processes underlying the transmission dynamics of infectious diseases; however, long-term morbidities associated with chronic or cumulative exposure are generally not incorporated into dynamic models for NTDs. Here we consider the complexities and challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematodiasis. We explore potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models, and consider the insights such frameworks may bring in terms of policy-relevant projections for the elimination era. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

The economic evaluation of Cystic echinococcosis control strategies focused on zoonotic hosts: A scoping review.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic neglected tropical disease (zNTD) which imposes considerable financial burden to endemic countries. The 2021-2030 World Health Organization's roadmap on NTDs has proposed that intensified control be achieved in hyperendemic areas of 17 countries by 2030. Successful interventions for disease control, and the scale-up of programmes applying such interventions, rely on understanding the associated costs and relative return for investment. We conducted a scoping review of existing peer-reviewed literature on economic evaluations of CE control strategies focused on Echinococcus granulosus zoonotic hosts. METHODOLOGY/PRINCIPAL FINDINGS: Database searches of Scopus, PubMed, Web of Science, CABI Direct and JSTOR were conducted and comprehensively reviewed in March 2022, using predefined search criteria with no date, field or language restrictions. A total of 100 papers were initially identified and assessed for eligibility against strict inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Bibliography review of included manuscripts was used to identify additional literature. Full review of the final manuscript selection (n = 9) was performed and cost data for control interventions were extracted. CONCLUSIONS/SIGNIFICANCE: There are very little published data pertaining to the cost and cost effectiveness of CE control interventions targeting its zoonotic hosts. Data given for costs are often incomplete, thus we were unable to perform an economic analysis and cost effectiveness study, highlighting a pressing need for this information. There is much scope for future work in this area. More detailed information and disaggregated costings need to be collected and made available. This would increase the accuracy of any cost-effective analyses to be performed and allow for a greater understanding of the opportunity cost of healthcare decisions and resource allocation by stakeholders and policy makers for effective and cost-effective CE control.

Immunodiagnosis of cystic echinococcosis in livestock: Development and validation dataset of an ELISA test using a recombinant B8/2 subunit of Echinococcus granulosus sensu lato.

The accuracy of screening tests for detecting cystic echinococcosis (CE) in livestock depends on characteristics of the host-parasite interaction and the extent of serological cross-reactivity with other taeniid species. The AgB8 kDa protein is considered to be the most specific native or recombinant antigen for immunodiagnosis of ovine CE. A particular DNA fragment coding for rAgB8/2 was identified, that provides evidence of specific reaction in the serodiagnosis of metacestode infection. We developed and validated an IgG Enzyme Linked Immunosorbent Assay (ELISA) test using a recombinant antigen B sub-unit EgAgB8/2 (rAgB8/2) of Echinoccocus granulosus sensu lato (s.l.) to estimate CE prevalence in sheep. A 273 bp DNA fragment coding for rAgB8/2 was expressed as a fusion protein (∼30 kDa) and purified by affinity chromatography. Evaluation of the analytical and diagnostic performance of the ELISA followed the World Organisation for Animal Health (OIE) manual, including implementation of serum panels from: uninfected lambs (n = 79); experimentally infected (with 2,000 E. granulosus s.l. eggs each) sheep with subsequent evidence of E. granulosus cysts by necropsy (n = 36), and animals carrying other metacestode/trematode infections (n = 20). The latter were used to assess the cross-reactivity of rAgB8/2, with these animals being naturally infected with Taenia hydatigena, Thysanosoma actinioides and/or Fasciola hepatica. EgAgB8/2 showed cross-reaction with only one serum sample from a sheep infected with Ta. hydatigena out of the 20 animals tested. Furthermore, the kinetics of the humoral response over time in five 6-month old sheep, each experimentally infected with 2,000 E. granulosus s.l. eggs, was evaluated up to 49 weeks (approximately one year) post infection (n = 5). The earliest detectable IgG response against rAgB8/2 was observed in sera from two and four sheep, 7 and 14 days after experimental infection, respectively. The highest immune response across all five animals was found 16 to 24 weeks post infection.

Development of a dose-response model for porcine cysticercosis.

Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods ("Proglottids", "Eggs", "Beetles" and "Carotid"). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the "Eggs" pathway and a merged "Oral" pathway combining the "Proglottids", "Eggs" and "Beetles" pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.

Modelling diagnostics for Echinococcus granulosus surveillance in sheep using Latent Class Analysis: Argentina as a case study.

Echinococcus granulosus sensu lato is a globally prevalent zoonotic parasitic cestode leading to cystic echinococcosis (CE) in both humans and sheep with both medical and financial impacts, whose reduction requires the application of a One Health approach to its control. Regarding the animal health component of this approach, lack of accurate and practical diagnostics in livestock impedes the assessment of disease burden and the implementation and evaluation of control strategies. We use of a Bayesian Latent Class Analysis (LCA) model to estimate ovine CE prevalence in sheep samples from the Río Negro province of Argentina accounting for uncertainty in the diagnostics. We use model outputs to evaluate the performance of a novel recombinant B8/2 antigen B subunit (rEgAgB8/2) indirect enzyme-linked immunosorbent assay (ELISA) for detecting E. granulosus in sheep. Necropsy (as a partial gold standard), western blot (WB) and ELISA diagnostic data were collected from 79 sheep within two Río Negro slaughterhouses, and used to estimate individual infection status (assigned as a latent variable within the model). Using the model outputs, the performance of the novel ELISA at both individual and flock levels was evaluated, respectively, using a receiver operating characteristic (ROC) curve, and simulating a range of sample sizes and prevalence levels within hypothetical flocks. The estimated (mean) prevalence of ovine CE was 27.5% (95%Bayesian credible interval (95%BCI): 13.8%-58.9%) within the sample population. At the individual level, the ELISA had a mean sensitivity and specificity of 55% (95%BCI: 46%-68%) and 68% (95%BCI: 63%-92%), respectively, at an optimal optical density (OD) threshold of 0.378. At the flock level, the ELISA had an 80% probability of correctly classifying infection at an optimal cut-off threshold of 0.496. These results suggest that the novel ELISA could play a useful role as a flock-level diagnostic for CE surveillance in the region, supplementing surveillance activities in the human population and thus strengthening a One Health approach. Importantly, selection of ELISA cut-off threshold values must be tailored according to the epidemiological situation.

How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases.

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals , an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models.

There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.